Studies of acute and subchronic systemic toxicity associated with a copper/low-density polyethylene nanocomposite intrauterine device

Abstract

IntroductionThe physiologic safety of devices and materials intended for clinical implantation should be evaluated. This study, a logical extension of our previous work, aimed to investigate the safety of a novel contraceptive device, the copper/low-density polyethylene nanocomposite intrauterine device (nano-Cu/LDPE IUD), through studies of its potential toxicity after acute and subchronic administration in mice and rats.MethodsFor the acute toxicity study, single 50 mL/kg doses of nano-Cu/LDPE IUD extracts were administered to mice via intravenous or intraperitoneal injection. General behavioral adverse effects, mortality, and body weights were evaluated for up to 72 hours. In the 13-week subchronic toxicity study, the nano-Cu/LDPE composite with 10-fold higher than the standard clinical dose was implanted subcutaneously into the dorsal skin of Wistar rats. The control group underwent a sham procedure without material insertion.ResultsDuring all acute study observation times, the biologic reactions of the mice in the nano-Cu/LDPE group did not differ from those observed in the control group. The groups did not differ statistically in terms of body weight gain, and no macroscopic changes were observed in any organs. In the subchronic study, no clinical signs of toxicity or mortality were observed in either the nano-Cu/LDPE or control group during the 13-week period. The nano-Cu/LDPE composite did not cause any alterations in body weight, food consumption, hematologic and biochemical parameters, or organ weight relative to the control for any observed sample group. Histopathologic examinations of the organs revealed normal architecture, indicating that the inserted material did not cause morphologic disturbances in the rats.ConclusionOverall, the results indicate that the nano-Cu/LDPE IUD did not induce systemic toxicity under experimental conditions of the recommended standard practices, suggesting that the novel material IUD is safe and feasible for future contraceptive applications.

Antibacterial Activity and Cytocompatibility of Bone Cement Enriched with Antibiotic, Nanosilver, and Nanocopper for Bone Regeneration

“…With regards to the cytocompatibility, the data on biopolymers containing Cu are scarce. The report on nanoCu/low-density polyethylene nanocomposite intrauterine device indicated the possibility of using nanoCu without systemic toxicity [73]. Furthermore, in the study with no nanometric Cu, the growth of pre-osteoblast cells and their differentiation was observed [72,74].…”

Contraceptive Technologies: Looking Ahead to New Approaches to Increase Options for Family Planning

“…One approach is altering the delivery profile for copper by lowering the doses or release of copper ions from the IUD or integrating copper nanoparticles in the device to decrease the burst of copper release. 12,13 Another approach is to add an additional active pharmacologic ingredient (API) with the goal of improving the bleeding profile, either in terms of volume, frequency, or predictability. An example of this is a copper IUD that releases indomethacin, 14 a nonsteroidal antiinflammatory drug.…”

“…IUDs are a great example where significant investment is working toward enhancing the design for a range of clients including adolescents and women immediately postpartum and altering the formulation to reduce side effects and improve safety. One approach is altering the delivery profile for copper by lowering the doses or release of copper ions from the IUD or integrating copper nanoparticles in the device to decrease the burst of copper release 12,13. Another approach is to add an additional active pharmacologic ingredient (API) with the goal of improving the bleeding profile, either in terms of volume, frequency, or predictability.…”

Contraception au futur

“…Un système reposant sur l'insertion d'un fil porteur de petites « perles » de cuivre, qui reprend une forme sphérique lors de son insertion dans l'utérus, est commercialisé en France (Ballerine®) [21]. Une approche, qui consiste à intégrer le cuivre dans des nanoparticules, permet, quant à elle, d'éviter le pic de libération initial de cuivre lors de l'insertion du système [22,23]. Une autre méthode inclut un principe actif limitant les saignements dus à la réaction inflammatoire induite par le cuivre.…”